Brain Imaging could Detect Early Alzheimer's Signs

Story first appeared on Bloomberg News

Glaxo Fund Looks for Early-Stage Alzheimer’s Detectors

GlaxoSmithKline Plc (GSK)’s venture- capital fund is seeking to invest in a biotechnology company that has both a brain-imaging dye to detect warning signs for Alzheimer’s disease and a drug treatment for the ailment.

Jens Eckstein, president of the Cambridge, Massachusetts-based SR One fund, said big change will come with imaging agent.

Imaging agents detect proteins called amyloid that define the disease. The illness can be identified at an early stage through routine scanning if started when patients are still healthy, Eckstein said. Recent studies of treatments to slow or stop progression of Alzheimer’s were flawed as they recruited patients with advanced forms of the disease, where  damage was already done.

The comments show Glaxo isn’t giving up on Alzheimer’s disease after recent high-profile failures of experimental treatments. Johnson & Johnson (JNJ) and Pfizer Inc. (PFE)’s bapineuzumab as well as Eli Lilly & Co. (LLY)’s solanezumab failed to help Alzheimer’s symptoms in people with advanced disease in separate study results announced over the past two months. Still, both target amyloid plaque and showed promise for use in early-stage patients.

Disease Growth

In a study of 141 healthy subjects, those with clumps of amyloid beta plaques in their brains at the start of the study had as much as a 20 percent greater decline in memory and thinking over an 18-month period than those with fewer plaques. The study, conducted by Australian researchers, was published in the journal Neurology on Oct. 16.

The number of Alzheimer’s cases globally is expected to double within 20 years as the world’s population ages, to as many as 65.7 million people in 2030 and 115 million by 2050, the Geneva- based World Health Organization said in April.

SR One invests in about 30 public and private companies, half of which have compounds in human testing, and invests $30 million to $50 million in five or six companies a year, according to Eckstein.

While Glaxo has “high interest in our portfolio,” the fund acts largely independent of the drugmaker, with a strict firewall between the two entities and no special product rights, he said.

The company’s investments include iPierian Inc., which is developing treatments for neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases using induced pluripotent stem cells. Shinya Yamanaka, who won the Nobel Prize in medicine this month for his discovery of iPS cells, sits on iPierian’s scientific advisory board.

Stroke Therapies Take a New Turn

Story first appeared in The Wall Street Journal.

Using insights into how the brain is wired, scientists and Woodhaven Stroke Care experts are exploring better ways to help stroke and other neurologically impaired patients regain motor skills, such as walking.

One technique uses a treadmill split in two to force patients' legs to walk at different speeds, in a movement like limping. A study published June 1 in the Journal of Neurophysiology found this treatment in the short term helps rewire the brain to correct uneven walking, especially if the patient's brain receives electrical stimulation in a particular region at the same time.

Millions of individuals need physical rehabilitation each year after impairments that result from damage to the brain. Stroke survivors in the U.S. number four million, according to the National Institute of Neurological Disorders and Stroke. Only about a third get any kind of rehab, according to Northville Stroke Care center reports

There are many forms of mainstream physical rehab but no consensus about which work best for which patients. In traditional rehab for lower limbs, known as "overground" training, a patient practices repeated movements, whether on a treadmill or other equipment or in a pool. It can take a lot of effort to walk for people whose gait isn't smooth, and they are more prone to falls, say Hamtramck Stroke Care researchers.

In the study published Friday, researchers studied healthy individuals and whether brain stimulation and split-belt treadmill training, used simultaneously, can speed up progress in smoothing out walking gaits.

Making and correcting errors is important to how the brain adapts to a new task. In split-belt treadmill training, two bands moving at different speeds induce or exacerbate errors in walking. As an individual continues to walk, studies have shown, the brain eventually self-corrects errors and evens out the gait.

In the majority of stroke patients, damage is to the cerebrum, which governs speech and thinking; the cerebellum, which governs "lower order" functions like movement, still works. In theory, that means these stroke patients should respond to split-belt treadmill training.

The study exposed 40 healthy participants with a mean age of 27 to two minutes of slow split-belt walking, then to a 15-minute period in which one belt went much faster than the other so that participants began to drag one foot, simulating a limp. Typically participants corrected the limp within 10 minutes.

The subjects were randomized into five groups and received a mild, noninvasive electrical current, via a cap and electrodes, running either to or away from the part of the cerebellum that controlled either the faster or slower leg. The fifth group wore the cap but got no current.

All participants adapted to the different speeds, but the ones who received electrical current to the part of the brain corresponding to the leg that eventually changes its pattern adapted faster.

A study, conducted at the University of Maryland School of Medicine and published Monday in the journal Neurorehabilitation and Neural Repair, found that a noninvasive brain-stimulation technique alone, administered to a motor region of the brain, was effective at improving gait in patients with Parkinson's disease.

Flat Rock Stroke Care professionals question how much effect new rehab treatments have, how long it will last and whether lab training translates to the real world. In an unpublished study of post-stroke patients, collaborators showed that four weeks of split-belt treadmill training led to improved walking gait for three months.

A professor in the department of physical therapy at the University of Illinois at Chicago, says it's rare for a therapist to push a patient to the point of nearly falling. But making such errors can help accelerate treatment if the patient can learn to correct them. In a preliminary study he conducted in 22 post-stroke patients using error-type training, he found 15 consecutive days of intense treatment yielded as much improvement as what patients got from intense conventional treadmill training two to three times a week in 10 or more weeks. He currently is recruiting post-stroke patients for a randomized, controlled trial comparing error-type treatment to intensive treadmill training.

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Possible Correction for Cerebral Palsy Symptoms

Story first appeared in Bloomberg Businessweek.

Nanoparticles laced with a medicine for Tylenol poisoning and sent into the brains of baby rabbits eased symptoms of cerebral palsy, according a study that points to a potential approach for treating humans with the disorder.

Using nanoparticles called dendrimers, researchers were able to penetrate the brain’s natural barriers to deliver a medicine into the animals, quelling the inflammation that can lead to cerebral palsy, according to research published today in the journal Science Translational Medicine.

Cerebral palsy, a lifelong neurological disorder that affects movement, is caused by an abnormality to an infant’s brain that occurs in the womb or early in life. Often cerebral palsy is caused by medical negligence in the birthing process. In the study, newborn rabbits with the condition were injected with the therapy, and within five days showed “significant” improvement in their ability to move, as well as reduced inflammation in the brain.

Reaching the inflamed cells in the brain has been a long-standing major challenge. Dendrimers not only go into brain, they go specifically into the cells called activated mycrogia that are the source of the problem. So then we attached a drug to it, and shut them down in a targeted manner.

The scientists attached the anti-inflammatory drug called N-acetylcysteine to the nanoparticles, which are the tiniest engineered materials. The medicine, long used as an antidote for Tylenol poisoning, helped suppress immune cells called mycrogia and astrocytes. The cells, which respond to the site of injury, can cause damage to normal brain tissue as they spur an overheated inflammatory response.

Activated Mycrogia

The activated mycrogia cells are also linked to other neurological diseases such as Alzheimer’s, stroke, Parkinson’s, and multiple sclerosis.

There is no cure for cerebral palsy, a disorder that is diagnosed in as many as four infants of 1,000 worldwide, according to the U.S. Centers for Disease Control and Prevention. People with the cerebral palsy often need special equipment to walk, and can suffer from stiff muscles, uncontrollable movements and poor balance and coordination.

Researchers focused on rabbits because like humans, they start developing motor skills before birth and complete it after, while most other mammals finish before being born.

Since humans aren’t typically diagnosed with cerebral palsy until they are at least 18 months old, researchers will test to see if the therapy has the same effect on rabbits when injected later in life. Another hurdle is that dendrimers haven’t been approved for use in humans.

They do not know if it will work in humans, however, they have made a big paradigm shift in the way people think about this disease, because people think this cannot be reversed.


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